Cells must rewire their metabolic programs to satisfy changes in nutrient supply or energy demand. Mitochondria confer this flexibility that allows for survival in a changing environment. Cancer cells exploit this mechanism to escape cell death and survive in adverse conditions such as starvation or chemotherapy. To achieve this, we will focus on two key questions: A) How does the nutrient gradient shape mitochondria structure and function? and B) What are the signaling pathways linking metabolic sensing and mitochondrial function? Unraveling the mechanisms underlying metabolic sensing and adaptation, offer insights into basic biological mechanisms, their implications in cellular transformation and provide the foundation for novel diagnostic and clinical applications in cancer research.